Three month inhalation exposure to low-level PM(2.5) induced brain toxicity in an Alzheimer’s disease mouse model

Although numerous epidemiological studies revealed an association between ambient fine particulate matter (PM(2.5)) exposure and Alzheimer’s disease (AD), the PM(2.5)-induced neuron toxicity and associated mechanisms were not fully elucidated. The present study assessed brain toxicity in 6-month-old female triple-transgenic AD (3xTg-AD) mice following subchronic exposure to PM(2.5) via an inhalation system. The treated mice were whole-bodily and continuously exposed to real-world PM(2.5) for 3 months, while the control mice inhaled filtered air. Changes in cognitive and motor functions were evaluated using the Morris Water Maze and rotarod tests. Magnetic resonance imaging analysis was used to record gross brain volume alterations, and tissue staining with hematoxylin and eosin, Nissl, and immunohistochemistry methods were used to monitor pathological changes in microstructures after PM(2.5) exposure. The levels of AD-related hallmarks and the oxidative stress biomarker malondialdehyde (MDA) were assessed using Western blot analysis and liquid chromatography-mass spectrometry, respectively. Our results showed that subchronic exposure to environmental levels of PM(2.5) induced obvious neuronal loss in the cortex of exposed mice, but without significant impairment of cognitive and motor function. Increased levels of phosphorylated-tau and MDA were also observed in olfactory bulb or hippocampus after PM(2.5) exposure, but no amyloid pathology was detected, as reported in previous studies. These results revealed that a relatively lower level of PM(2.5) subchronic exposure from the environmental atmosphere still induced certain neurodegenerative changes in the brains of AD mice, especially in the olfactory bulb, entorhinal cortex and hippocampus, which is consistent with the nasal entry and spreading route for PM exposure. Systemic factors may also contribute to the neuronal toxicity. The effects of PM(2.5) after a more prolonged exposure period are needed to establish a more comprehensive picture of the PM(2.5)-mediated development of AD.